John Zaunders1, Wayne B Dyer, Melissa Churchill. 1. aCentre for Applied Medical Research, St. Vincent's Hospital, University of New South Wales, Australia. j.zaunders@amr.org.au
Abstract
PURPOSE OF REVIEW: The Sydney Blood Bank Cohort comprised eight individuals who were infected with an attenuated, nef/LTR-deleted strain of HIV-1 from a single donor. All six recipients with sufficient follow-up, as well as the donor, were long-term nonprogressors. Only three recipients have maintained undetectable plasma viral loads, allowing investigation of factors that determined elite control of attenuated HIV-1 infection. RECENT FINDINGS: Follow-up of recipients showed that infection with this attenuated HIV-1 strain resulted in either low or absent viral replication in vivo for up to 29 years. The three patients without detectable viraemia have been studied for virological, genetic and immunological correlates of elite control. CD4 proliferation in vitro in response to p24 provided the clearest distinction of elite controllers from the slow progressors. Host factors are believed to differentiate the three elite controllers; only one, C135, has identifiable genetic polymorphisms that probably contributed to nonprogression: Δ32 CCR5 heterozygosity, HLA-B57 and HLA-DR13 alleles, in addition to infection with nef-defective HIV-1. SUMMARY: Even nef-defective HIV-1 can lead to sufficient replication in vivo to enable viral evolution and eventual progression to immunodeficiency. Host factors modified the outcome of infection with attenuated HIV-1, as exemplified by the unique patient C135.
PURPOSE OF REVIEW: The Sydney Blood Bank Cohort comprised eight individuals who were infected with an attenuated, nef/LTR-deleted strain of HIV-1 from a single donor. All six recipients with sufficient follow-up, as well as the donor, were long-term nonprogressors. Only three recipients have maintained undetectable plasma viral loads, allowing investigation of factors that determined elite control of attenuated HIV-1 infection. RECENT FINDINGS: Follow-up of recipients showed that infection with this attenuated HIV-1 strain resulted in either low or absent viral replication in vivo for up to 29 years. The three patients without detectable viraemia have been studied for virological, genetic and immunological correlates of elite control. CD4 proliferation in vitro in response to p24 provided the clearest distinction of elite controllers from the slow progressors. Host factors are believed to differentiate the three elite controllers; only one, C135, has identifiable genetic polymorphisms that probably contributed to nonprogression: Δ32 CCR5 heterozygosity, HLA-B57 and HLA-DR13 alleles, in addition to infection with nef-defective HIV-1. SUMMARY: Even nef-defective HIV-1 can lead to sufficient replication in vivo to enable viral evolution and eventual progression to immunodeficiency. Host factors modified the outcome of infection with attenuated HIV-1, as exemplified by the unique patient C135.
Authors: Mark A Brockman; Denis R Chopera; Alex Olvera; Chanson J Brumme; Jennifer Sela; Tristan J Markle; Eric Martin; Jonathan M Carlson; Anh Q Le; Rachel McGovern; Peter K Cheung; Anthony D Kelleher; Heiko Jessen; Martin Markowitz; Eric Rosenberg; Nicole Frahm; Jorge Sanchez; Simon Mallal; Mina John; P Richard Harrigan; David Heckerman; Christian Brander; Bruce D Walker; Zabrina L Brumme Journal: J Virol Date: 2012-04-11 Impact factor: 5.103
Authors: Richard Apps; Zhaojing Meng; Gregory Q Del Prete; Jeffrey D Lifson; Ming Zhou; Mary Carrington Journal: J Immunol Date: 2015-03-09 Impact factor: 5.422
Authors: Wei Zou; Paul W Denton; Richard L Watkins; John F Krisko; Tomonori Nochi; John L Foster; J Victor Garcia Journal: Retrovirology Date: 2012-05-28 Impact factor: 4.602